The goal of the human cancer immunologist is to understand the immunobiology of the tumor-host relationship. It is from a correct perception of his relationship that the highly desirable objective of immunological prevention or therapy of neoplastic disease will come. This can be accomplished only if we first establish that tumor specific antigens exist in human cancer. Tumor specific antigens are now demonstrable in nearly all animal tumors that have been adequately studied. Recent studies by Carey et al. and others (1-4) have shown that tumor distinctive markers which have antigenic activity in the tumor-bearing patient also exist. We now propose to use the same approach, called autologous serologic typing, to study a very prevalent form of human cancer - squamous cell carcinoma. To define characteristic tumor antigens in human squamous carcinoma, we will: establish a comprehensive serum bank containing serial serum specimens from many patients; establish new cell lines of human squamous carcinoma and corresponding normal fibraoblasts from the same patients; preserve in our cell bank at early passage all new cultures; characterize as completely as possible all new cell lines and make them available for study by others; survey the autologous serum-tumor cell combinations with sensitive mixed hemadsorption and immune adherence assays for antibody reactive with cell surface antigens; and establish antibody specificity and antigen distribution by adsorption analysis. The development of new human squamous cell carcinoma culture lines will be a primary objective. To achieve this objective, we will 1) make use of our large patient population and the many tissue speciments available; 2) stress the use of biopsied tissue from recurrent or metastatic tumor deposits; 3) examine the usefulness of different growth media; 4) test human cord blood serum as a source of growth factors; 5) use media selective for non-fibroblast cell types and; 6) use nude mice to select the tumor cell populations from mixed cultures and to confirm that the cultured cells are tumor derived.